Drug Delivery Strategies for Tolerogenic Therapy for Autoimmune Diseases in an Antigen-Specific Manner

Kevin J. Peine (The University of North Carolina at Chapel Hill, USA), Naihan Chen (The University of North Carolina at Chapel Hill, USA), Eric M. Bachelder (The University of North Carolina at Chapel Hill, USA) and Kristy M. Ainslie (The University of North Carolina at Chapel Hill, USA)

Abstract

Autoimmune diseases are the result of an improper immune response towards a self-antigen. Predominantly, autoimmune diseases have been treated using therapies that suppress systemic immune responses, which can result in significant side-effects like increased risk of infection and cancer. Alternatively, induction of immune tolerance through antigen-specific therapies can inhibit disease-associated responses without systemic suppression. Previously, immune tolerance has been accomplished by soluble antigen delivery through oral, nasal or sublingual routes. However, these therapies have shown minimal success in clinical settings. In an attempt to increase the efficacy of these therapies, recent work has utilized microparticulate delivery vehicles for the induction of immune tolerance. Microparticles are capable of increasing the solubility and circulation of cargo. In addition, their ability to passively target macrophages and dendritic cells increases their capacity for modulating the immune response. Recent work has shown microparticles fabricated with disease-associated antigens have limited disease progression and severity in animal models of Multiple Sclerosis, Type 1 Diabetes and Rheumatoid Arthritis. Inhibition of disease progression has corresponded with an antigen-specific decrease in inflammatory responses. The emerging field of inducing tolerance through microparticle-based therapies can limit therapeutic side-effects and increase patient quality of life by providing for long-term suppression of autoimmune disorders without compromising systemic immune function.

Introduction

Autoimmune Diseases

According to the National Institutes of Health (NIH), approximately 23.5 million Americans are living with at least one autoimmune disease. These diseases, which can occur in almost any tissue, are the result of an improper immune response towards self-antigens. In some cases, such as systemic lupus erythematosus (SLE), the immune response mounts a response that targets multiple healthy tissues, while others like Multiple Sclerosis (MS), Type-1 Diabetes (T1D) or Rheumatoid Arthritis (RA) are more organ or site specific. Current therapeutic strategies for autoimmune diseases provide amelioration of symptoms, most commonly through systemic immune suppression, but fail to treat the underlying causes of disease. Although autoimmune diseases manifest themselves very differently, a number of current therapeutics have similar strategies for immune suppression, including inhibition of T cells, B cells, and pro-inflammatory cytokines. This chapter will discuss a number of therapeutic approaches for common autoimmune diseases, as well as the emerging field of nano/microparticulate therapeutics for the treatment of autoimmune diseases.